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Dr Gopal RamuMedical Research

Notes

Dr Gopal Ramu (1924-2003) was a noted Indian leprologist. He played a key role in building up research at CLTRI (Central Leprosy Teaching and Research Insititute) from 1962-76 and the Central JALMA Institute for Leprosy Research (CJIL) from 1976-86. He spent his last years with his daughter at Coimbatore (Tamilnadu) where he continued to advise on leprosy research.

The following is an interview given by Dr G Ramu, ‘An Autobiographical Sketch’, in The Indian Leprologists Look Back. Bombay, 1990, pp. 105-115.

"I was born in Alleppey in Kerala in 1924 as the last of a family of 6 children.

In 1937 my family migrated to Indore where my eldest brother, after passing out of the University, got employed. I attended the Jain High School at Tudore. In this High School besides the formal education the study of the Jain religion was compulsory; this religion prescribes love and compassion for all living beings and made a deep impression on me.

I had my medical education in the King Edward Medical School at Indore. In 1942 when I was in the second year I was arrested along with several other students for taking part in the Quit India Movement.

In 1953, I joined the MGM Medical College in Indore after earning just enough money to see me through my graduation in 1955. Similarly I completed my Postgraduate degree in 1973 while in service at CLTRI Chingleput.

I served in the Holkar State in various places and in the Tuberculosis Clinic and Hospital at Indore for 6 years from 1946 onwards. I joined the TB Clinic at a time when TB was dreaded as a fell disease. With the advent of Streptomycin, INH and PAS, tuberculosis lost much of its terror. Drug treatment along with Surgery changed the outlook for TB patients. I particularly value my close relationship with the late Dr. Bordia, the tuberculosis specialist in the Clinic who later became the Director of the National Institute of Tuberculosis and then Adviser on Tuberculosis to the Government of India. Besides learning the subject from Dr. Bordia, I also observed that his sympathy for the patients altered the psychological attitude of the patients to an extent which was responsible in no small measure for the cure of their disease.

I undertook the Tuberculin Survey of Indore which brought out that social factors like crowded dwellings, dusty occupation, lack of sunlight, lack of elementary hygiene and malnutrition were responsible for the high infectivity rates, as measured by the positive tuberculin reaction. This was followed by the mass BCG vaccination program in Indore with which I was closely connected.

The people and circumstances that stimulated me to work in leprosy…

When I was serving in a tea plantation in South India in 1955 soon after graduation I encountered a case of ulcerating reversal reaction I saw that leprosy offered a challenge just as TB had done earlier. I took this up. I visited a leprosy study centre at Tirukoilur and the Lady Willingdon Leprosy Sanatorium, Chingleput. The visits strengthened my resolve.

I joined as Assistant Surgeon in charge of Leprosy Surveys in Madhya Bharat, Indore. While at Indore, Dr. S. K. Mukerjee who had been my Professor of Medicine during both the periods of my medical education encouraged me, allowing me to conduct a leprosy clinic in the Cardiology Department of the MY Hospital on Sundays. He also stimulated me to carry out special studies. The study of the blood supply of the median and the ulnar nerves was carried out by me in the Department of Anatomy of the MGM Medical College with the collaboration of Dr. Hussein.

I was transferred to Rewa as the Medical Officer of a Leprosy Pilot Project in 1956, where Dr. Mrs. T. Ganapathy medical specialist in the General Hospital and Dr. C. Gopalan the then Director General of ICMR gave me permission to collaborate with Dr. V. Nagarajan, the biochemist in the ICMR Lathyrism Enquiry Unit. We carried out studies on the protein and lipid profiles of leprosy patients and highlighted the decreased cholesterol levels and increased copper levels in the serum of lepromatous leprosy patients. I obtained the cooperation of villagers whom I had contacted before entering on the work. We also obtained help from the Khadi and Village industries Board and the Agricultural Department.

The Leprosy Pilot Project participated in controlling the cholera epidemic in different parts of the District. Dr. Dwivedi who was in the Lathyrism Enquiry unit almost formed part of the team. Lathyrism was an important problem in this area, hence we had a close rapport with the population.

Hospitalisation was offered in the General Hospital to treat reactional states. The Khadi and Village Industries Department helped the villagers with bee keeping. Besides obtaining honey, the villagers used the beeswax for anointing the dry and icthyotic feet and had freedom from cracks in the soles of the feet and. skin. They were getting an effective drug Dapsone for the first time and the results were very gratifying. The villagers of Rewa and Dewas Districts benefited enormously. The coverage was complete with regard to case detection, case holding and. contact surveillance.

Dr. C. G. S. Iyer of the Indian Cancer Research Centre visited Rewa in 1960 as a member of the Lathyrism Enquiry Committee and I had the occasion to go to the field with him to see cases. Impressed with the work in leprosy, he induced me to go over to CLTRI as a Junior Scientific Officer in 1962 where he became the Deputy Director of the Laboratory Division of CLTRI. In CLTRI, I came into contact with Dr. K. Ramanujam and Dr. Dharmendra who were responsible for my work in clinical leprosy. I also came in contact with Dr. Cochrane who used to motor down from Vadathorasalur on Saturdays, and used to see cases and discuss them with Dr. Ramanujam and me. In 1964 I had the occasion to attend on Dr. H. W. Wade who used to have cardiac asthma at night. Despite this he used to see patients during the day. I showed him cases of histoid leprosy which were different from the ones he had described. He called them the Madras variety of histoids in one of his papers with Dr. Ramanujam prior to his demise in 1965.

My wife has been a dependable companion through three and a half decades of an impecunious life of leprosy research.

My principal contributions to Leprosy....

I have been interested in the reactional states. A chance observation in Rewa in 1956 that chloroquine relieved ENL in a female patient to whom it was given as a treatment for amoebic hepatitis led me to use it in the treatment of reactions. Subsequently the study of chloroquine was undertaken at JALMA where chloroquine was found to be suppressive of complement activation, to inhibit platelet aggregation, increase fibrinolytic activity, prevent fibrinogen conversion to fibrin and suppress antigen-induced lymphocyte response. Further work is in progress to use chloroquine as one of the constituents in a regimen for the treatment of reactions in Kumbakonam

I contributed chapters on acute exacerbations, systemic involvement and prognosis in Dharmendra’s book on leprosy; and on management of reactions in the book, Window on Leprosy. Research work is mostly team work. Among the papers, which number over 250, there are several with combined authorship. The co-authors include young scientists and medical students who carried out studies during their elective period. I worked in elucidating the course of events following the entry of M. Leprae into the human host, amongst contacts. This was carried out at first in CLTRI with a follow-up of 10 years of lepromin negative and positive children. This was continued in Agra along with serological tests for identifying sub-clinical infection, viz., FLA-ABS and SACT tests. We found that, amongst contacts, humoral immunity appears to respond first by positivity in both FLA-ABS and SACT tests. This was later followed by the response of cell mediated immunity. Whereas FLA-ABS appears to be positive in a large number of contacts only l0-20% are positive in the SACT test. In children who have antibodies to MLO4, leprosy appeared within a year, thus the SACT test has a. pre-clinical portent. It they develop BT or TT disease or they become Mitsuda positive, the antibodies tended to disappear. It is possible that if the antibodies continue to be present the individual may develop serious forms of the disease. In recent studies Kumbakonam SACT positivity seems to distinguish relapses from reversal reactions with which it may be confused.

Another contribution in which Dr. V. D. Ramanathan, a young immunologist played a major part is a longitudinal study of eases of leprosy with regard to the development of reactive states by estimating immune complexes and their solubilisation in order to forecast the occurrence of a reactional state. The lack of immune complex solubilisation seems to indicate reaction proneness. It has been a very pleasant experience to work with young scientists. The scientists developed a kinship with me by suggesting directions of research with clinical support. Observing patients gave non-clinical scientists emotional satisfaction that they were contributing to the cause of removing human suffering.

During the course of working for nearly n quarter of a century in 2 premier research institutions, i.e. CLTRI and CJIL, and contacts with institutions like the Foundation for Medical Research, Bombay, the All India Institute for Medical Sciences, New Delhi etc, I had the opportunity of observing young scientists working in different disciplines from a close range. The disciplines included epidemiology, immunology, biochemistry and microbiology besides the allied department of Surgery. It is uncommon to find scientists who understand the place of their research in the entire perspective of the disease, plan their experiment, master the technique and are keen in the reproducibility of their results. Two such scientists are Dr. U. Sengupta, Deputy Director for Immunology, JALMA and Dr. V. D. Ramanathan, Senior Research Officer, Tuberculosis Research Centre, Madras, Some others though very good in their respective fields tend to have a tubular vision while doing a particular experiment and having finished it switch on to another. Good scientists are emotionally different from laymen. They strive for achieving a goal without caring for material benefits. They have to be fostered by providing for their scientific needs in equipment and other resources. They need also recognition as much as a child needs love. Unfortunately this does not obtain in the scientific culture of our country.

Bias in research may lead to suspicion about the honesty of the whole scientific community. A work on the culture of M. leprae was all but hailed as a breakthrough. Work in two laboratories involving money and time did not corroborate this claim

As a Project Officer of the Damien Foundation Project in Deeg I have the gratifying experience of how close contact with the community gives invaluable help in all the components of the control programme. There was a pocket of hyperendemicity in and around a village called Titpuri in the Lakshmangarh Tehsil of Alwar District of Rajasthan. On the occasion of anti-leprosy day when invitations were extended to all the Panchayat members of the villages around Titpuri who attended the meeting in strength. After giving a preliminary talk on leprosy an old man who was held in respect in these villages and who had been cured of leprosy was requested to address the members. He told them that he had leprosy and he was cured by the treatment as all could see. Therefore there was no need of being afraid of it. ...This was a direct message and was very effective. There was a question-and-answer session. The panchayat members asked very intelligent questions on the causation, spread and treatment of leprosy. On another occasion nearly the entire population of the villages had turned up in one place for being examined. Mr. LaPierre, one of the authors of Freedom at Midnight and other books was there during this survey. Struck by what he saw he announced the donation of the proceeds of the sale of his book, Freedom at Midnight, for antileprosy work in this area. However, he changed his decision later and donated this amount to Mother Theresa’s organisation in Calcutta.

Professional Life

My professional life has been described earlier as far as my service in various departments is concerned. I have been as much interested in the care of leprosy patients as in research. It is only when research can contribute to relieve sufferings of leprosy patients that I have taken to research in CLTRI as well as in CJIL Agra which are research oriented. While an Assistant Director in CLTRI in Chingleput I did not have much administrative work. Administrative work was involved in CJIL Agra.

Work in leprosy necessitates an appreciation of the progress in various disciplines. I was involved in the Epidemiology Unit at CLTRI, Chingleput, in the chemoprophylaxis trial and as a result had the opportunity to work on epidemiological studies on the incidence of leprosy amongst contacts. I was also a member of the Action Group on Leprosy Control. As member of the task Force on Leprosy Research of the ICMR, I identified areas where research was necessary and prepared protocols for research. As a member of the Working Group on the Strategy of Leprosy Eradication under Swaminathan, I had the satisfaction that the administration was serious about the task of leprosy eradication, though the treatment aspects and strengthening of the leprosy control units had been enforced, many of the recommendations remain to be implemented especially on the Rehabilitation and the Legal Aspects.

I have been the Resource person in several WHO Workshops conducted in various parts of the country such as Chingleput, Chandigarh, Lucknow, Baroda, Karbi Along, Sambalpur, Karigiri, Delhi and Salur. I have attended most of the IAL Conferences from 1962 onwards. I was a Consultant for CLTRI for a short period and a member of the Scientific Advisory Committee of CJIL Agra. I am involved in the Chemotherapeutic Drug trials at the Tuberculosis Research Centre for Leprosy as an independent assessor. My visits to several countries like UK, Burma, Thailand, Malaysia, Japan, Italy and Holland has led to the appreciation of the fact that leprosy is now attracting young scientists all over the world, and is no more the Cinderella of Medicine.

Participation in the Changing Profile of Leprosy

Classification of Leprosy: - The Classification of Leprosy used to be a subject for polemics in every conference national and international. Classification based on the immunological spectrum found in leprosy by Ridley and Topling in 1966 has considerably narrowed down the differences. However, tins classification depends on histology. The IAL has arrived at a Consensus Classification based on clinical grounds. Dr K V Desikan and I were asked to detail the histological and clinical features of the types based on the clinical pattern of the disease existing in India. Thus for the first time a classification has been prepared which has the clinical variations in view and which is based on immunologic and histologic findings. In this classification, leprosy has been divided into 5 types viz., Indeterminate, Tuberculoid, borderline, Lepromatous and Polyneuritic. Instead of vague statements definite clinical criteria were introduced e.g. Indeterminate and Tuberculoid lesions were put down as having a number of lesions not exceeding three. Macular lesions were recognised as of considerable importance and both Tuberculoid and Borderline Leprosy were divided into Macular and Infiltrated Lesion. Polyneuritic leprosy was recognised as a separate entity as in the former Indian Classification. In 1981 this Classification was adopted by IAL.

According to WHO for purposes of treatment leprosy has been divided into Multibacillary and Paucibacillary groups. In my study at Chingleput I found that despite skin smears being negative, cases with a large number of skin and nerve lesions and put down as BT had a bad prognosis in respect of relapses, neurological disabilities. Since placing them as Paucibacillary would lead to (1) early discharge from treatment even while the disease was active, (2) neglect of the deformity and also occurrence of fresh deformities, I proposed that cases with more than 10 lesions, and those with large lesions and more than 2 nerves involved, should be considered as Multibacillary for purposes of treatment. It is gratifying to note that under the NLEP cases with over 10 lesions have been taken as Multibacillary and recommended Multibacillary treatment. The Consensus on Treatment also was adopted by the IAL. Earlier, in JALMA, we had tried out Dapsone in cases of Tuberculoid leprosy and. found that stopping treatment at a point of time when cases became inactive did not lead to any increase in the relapse rate. Perhaps one of the important steps of the WHO towards leprosy eradication was the fixing of the regimen and the duration of the treatment in Paucibacillary leprosy.

This had led to a tremendous shedding of cases and bringing down the prevalence. The single great administrative leap forward was the inclusion of leprosy in the 20-point programme preceded by the Swaminathan Committee for evolving the Strategy of Leprosy Eradication. I am happy to have been on on the package of Treatment. The interest of the late Prime Minister Indira Gandhi was responsible for cutting administrative restraints. Under Dr C K Rao’s dynamic leadership uniform drug regimens and operational techniques are being followed throughout India.

The other disciplines in leprosy have not kept pace with the advances in treatment and the strategy for eradication. Generally sociology has been found to be lacking in the sense of urgency, the only exception being the formation of the Social Research Institute under the GMLF. It is necessary that the work of this Institute be enlarged to include all components of the Leprosy Eradication Programme.

Important incidents connected with Leprosy….

It is true to say that the breakthrough in leprosy research came with (1) the mouse foot pad inoculation in 1960 by Shepard, (2) the armadillo model in 1973 and (3) the advent of Rifampicin in the treatment of leprosy. The recommendation of fixed drug regimens by WHO for adaptation for mass therapy in 1981 can be considered to be a very important step in leprosy control. All these measures have changed the entire face of leprosy treatment. Leprosy research requires more inputs and understanding of certain immunologic phenomena. These are called the reactive states and are known to represent hyperactive immunological mechanisms. They are fraught with deforming sequelae. Prediction of reactive states and effective treatment continue to be challenging tasks.

In 1981, I was invited by the Japanese Leprosy Association as a Guest Lecturer for the 52 nd Japanese Leprosy Conference, along with Dr K V Desikan. The lecture was on the Indian Classification of Leprosy, which I compared to the Japanese, Madrid, Ridley and Jopling systems of classification. The Japanese dermatologists and scientists in other disciplines wanted to learn about the clinical manifestations since they felt that perhaps they were missing cases. I visited the Leprosy Sanatorium in Tokyo. The extreme crippling among the cases in the Sanatorium was startling. Their eyes were involved both indirectly due to lagophthalmos, and directly due to involvement of the anterior segment by M. leprae. They had alopecia of the scalp due to leprosy; triple nerve palsy was seen in the hands. They had dropped feet. No wonder that the Japanese are mortally afraid of the disease.

In 1981 I was presented the JALMA Oration Award for my work in the clinical and therapeutic fields.

I was invited by the APS University to deliver the University Extension Lecture in 1983, and by the IAL to deliver the Guest Lecture at the IAL Conference in 1985 which I did on the “Genesis of Leprosy Lesions”.

It has been a pleasure for me to examine doctoral thesis on leprosy work by the Bombay University which I found to be of very high standard.

I was Vice-president of IAL between 1983 and 1985.

Certain other aspects of leprosy….

There are areas in India where leprosy is a problem among certain ethnic groups.... For example the Bhils of Jhabua and other districts in Madhya Pradesh, the tribals of Sidhi district and the tribals all along the Kaimur Range as well as the Muslim population in Kadamath and Androth Islands of the Laccadives. A close study of their lives, housing, clothing, food habits, occupation, marriage customs and sleeping habits would throw light on the transmission of the disease. While genetic factors might have some influence on the type of the disease in these groups, much more than in the indigenous populations, problems other than genetic factors might be of very great importance in the epidemiology of leprosy amongst them. For example, endemic goitre is associated with leprosy amongst the tribals of Sidhi district. Prevalence of lepromatous leprosy is four times more in those who have goitre. Such a study will also give interesting insights into the knowledge, attitudes and practice as regards the disease in these closed communities. Health education will necessarily have to be tailored to the situation obtaining in these communities. Amongst the Bhils patients with disabilities are rejected and are observed to seek shelter in a colony in Dims District run by a Christian Mission. A visit to the colony shows how they were being exploited as agricultural labourers. The conditions of life and food requires in much improvement.

Persons working in leprosy cannot but be involved in the life of patients. Unlike other diseases the doctor-patient relationship is more intimate due to the prolonged course of the disease.

Victor had a stormy course of the disease while in CLTRI. He came out of the sanatorium bearing scars of the numerous ulcerating ENLs which he had suffered from. By dint of unsparing effort he passed out as a Tamil Vidwan from Annamalai University. He was appointed as a teacher in a Christian Mission High School in Madras. On the day he reported for joining the headmaster asked him about the cause of the scars. He told him in all his honesty that he had been an inmate of a leprosy Sanatorium. Thereupon the headmaster cancelled the appointment. I appealed to the Bishop who had exhibited compassion for the leprosy patients. It appeared as if he had seen reason when he called Victor to Madras, only to reject him. During my visit to London, I had a telephonic conversation with Group Captain Cheshire and wanted him to intervene. Victor was finally given a job in an institution where the children of leprosy patients were studying, thus saving him from recourse to suicide which he has considering as a last resort. Sir Chesterman, who was physician to Mahatma Gandhi when he was interned at the Aga Khan’s Palace and was carrying out the renovation of Dr Albert Schweitzer’s hospital, overheard my talk and was surprised that the thoughts of the patient were haunting me even when I was on tour.

In 1972 a patient belonging to the village Jarnouli in Bhind district could not bear the burden of a dependent and humiliating life as he was badly disabled. He requested his nephew to drown him in the river. The nephew approached the Panchayat members who were willing to carry out the request if the Police Department concurred. The Police Department saw no reason to disagree. The patient was as carried on a cot which was weighted and the patient was consigned to the flood waters. One of the members who carried this out was a Sarvodaya worker and told me the story. I kept him in Agra for a week and gave him the necessary health education about leprosy so that he could help the patients in at least taking treatment. He is at present doing laudable work amongst leprosy patients in this district.

Amongst the bizarre and cruel practices perpetrated by society against leprosy patients is one of pushing the patient into a bonfire lit during the Holi festival in Bijnor District in UP. However, the redeeming feature is the presence of individuals with a humane altitude who come to the aid of the afflicted. An army Major who could not stand the ghastly sight mentioned above to bring the patients to Agra for treatment. Patients from several districts in UP used to complain that they had been expropriated because of leprosy. Out of over a hundred letters addressed by me to the Collectors to bring this to their attention only two patients had a favourable response and had their land restored.

In the villages around Kumbakonam there is a pernicious custom amongst Muslims of divorcing their wives when they get leprosy. Persuasive health education should he targeted to this group.

Hobbies and Interests....

Having worked in leprosy for over three-and-a-half decades many of my hobbies are coloured by involvement in leprosy. I have always been interested in classical literature and art. Digging into Tamil literature I found that the earliest reference to leprosy is found in the literature of the first Sangam Period, i.e. 2nd. Century BC. This is found in the work of Kapilan Avaiyar, a Tamil poet whose poetry is very popular for simplicity and worldly wisdom, says in one of his poems, “Cruel poverty; more cruel is poverty in the prime of life: and most cruel of all is to suffer from incurable leprosy”. Perhaps he was the first to use the Tamil word “thozhu noi” in place of “Mahakushtam”. Nankeeran, a poet also in the Sangam Period, is said to have been cursed with leprosy for questioning the correctness of a poem written by Lord Shiva himself. Leprosy has gained a place in “Devaram” or Garland of Verses sung by Appar in the Seventh Century. He belonged to the present day South Arcot during the reign of King Mahendrapallava. Obviously this area had a high prevalence of leprosy even during this period. Leprosy is entrenched in tradition; the cause is attributed to curse or sin and is said to be incurable.

Such ideas cannot be removed by occasional attempts at health education. Talks are listened to, but rarely make a strong impact, entrenched as myths and rituals are in our social culture. Health education should therefore he sustained.

Future of Leprosy….

While introduction of MDT a very great step forwards, there are important problems connected with the approach.

The problems are (1) With the regimen; (2) Operational; (3) Rehabilitation.

In the initial stages of the introduction of MDT certain components of the eradication programme do not receive enough attention. One of these is case detection. It is well known most serious forms of the disease, that is the infiltrative form of lepromatous leprosy is not diagnosed early. They would continue to be sources of infection in the community. Therefore case detection has to be improved. Acute neuritis should be recognised and given adequate treatment both by drugs and physical measures.

The services of behavioural scientists should be available.

The field programme should be designed to suit the local conditions. Epidemiological evaluation and monitoring should also be planned by an independent assessment unit not connected with the state government. The coverage should be not less than 90%. Therefore there should be “micro-planning” at the level of the Leprosy Control Unit, and should be built upward to the district and to the state, and finally to the country.

The beginning of the End.

The Gita gives the message of Action without expecting the Fruit thereof. This message is of very great importance to scientists. Interpreting it for the scientists this would mean that a scientist should not orientate his investigation towards results. If he does so, he might miss important findings which are not in the direction of the results he expects. I am afraid that in some laboratories investigations are result-oriented.

For me work in leprosy itself has been self fulfilling. Perhaps I would have retired into oblivion but had to seek employment on account of the red-tapism resulting in inordinate delay in getting my pension. However, I am not sorry for this. In Kumbakonam I have found a congenial atmosphere for working with plenty of patients and willing workers. I have come into contact with Dr. Palande whom I had known earlier. He has done yeoman service to the cause of rehabilitation of disabled patients. What is unique about the rehabilitation in surgery of his is the very good follow up and the assessment of the working capacity of the patient. It gives a very good feedback for modification in surgical procedure. New drug regimens are being employed. The results appear to be gratifying both in reactive and active leprosy. In clinical aspects methods of early diagnosis are being standardised. “Nishkamakarma” does not have any end….This depends on one’s physical capacity.